Higher Rates of PMDD in Women with ADHD
A 2025 study found that 45% of women with ADHD also have PMDD - compared to 10% of women without ADHD (1-3).
This isn't a coincidence. They have overlaps in terms of brain-based mechanisms (neurotransmitter systems and neuroinflammation).
Saffron Extract for ADHD
Saffron extract has been tested in many clinical trials for ADHD (4-8), and here’s what the results are saying:
In adults:
Combining saffron plus Ritalin provided better outcomes for ADHD symptoms compared to placebo.
• Saffron did not significantly change the number of adverse effects compared to Ritalin only
• This shows that saffron can be effective on its own or an additive benefit to existing ADHD medication.
In children and teens:
• Efficacy of saffron extract alone matched the effectiveness prescription ADHD medication (methylphenidate or Ritalin)
• Saffron plus Ritalin worked better than Ritalin alone
• Saffron was particularly effective for hyperactivity and sleep quality.
Saffron Extract for PMDD
Saffron significantly reduced PMDD symptoms (9):
• Saffron was comparable to an antidepressant (fluoxetine) in improving PMDD symptoms
• It significantly outperformed placebo.
• There was a significantly higher number of adverse events in the fluoxetine group, showing that saffron has far better tolerability.
Importance of a Saffron Extract Supplement over the Spice
The bioactive compounds in saffron responsible for its effects are called safranal and crocin (see how they act on neurotransmitters below).
A saffron supplement should be standardised and tested for a consistent amount of these actives, containing at least 3.5% of them.
DITTO exceeds this threshold with 6.56%, which is very high quality and ensures you’re getting a therapeutic dose.
You won't find this standardisation in:
• Cooking saffron (highly variable compound content)
• Most generic saffron supplements (rarely tested or standardised)
How is Saffron Extract Working in our Brain? (10-15)
1. Modulating Serotonin and Dopamine
Saffron’s active components influence neurotransmitter activity in the brain. Saffron can increase serotonin availability, improving mood. Moreover, it promotes dopamine release, increasing motivation and the sensation of pleasure associated with reward.
Why this matters for PMDD: Women with PMDD have higher serotonin transporter binding, reducing available serotonin in synapses - which correlates with depressive symptoms (16). Saffron's ability to increase serotonin availability may directly counteract this mechanism, reducing symptoms in PMDD populations.
Why this matters for ADHD: People with ADHD typically have low baseline serotonin, which can contribute to symptoms of hyperactivity (restlessness). There is also a higher density of dopamine transporters and altered receptor availability, meaning that dopamine levels are always too low, or ineffective, which can lead to the inattention (difficulties concentrating) in ADHD (17). Saffron can stabilise these effects by acting on both neurotransmitter systems.
2. Inflammation
Saffron also has anti-inflammatory effects, by inhibiting the production of inflammatory chemicals and reducing cellular stress.
Why this matters: Interestingly, both ADHD and PMDD are associated with neuroinflammation. Saffron’s additive anti-inflammatory effects may provide additional therapeutic benefit for those with both (18-19).
3. Formation of New Neurones
Apart from neurotransmitter systems, saffron has been shown to increase levels of brain derived neurotrophic factor (BDNF), a protein that supports neuronal growth, survival, and synaptic plasticity, particularly in brain regions involved in mood regulation like the hippocampus.
Why this matters: This is an additional pathway through which saffron may improve mood and cognitive function beyond neurotransmitter modulation.
The Takeaway
Both ADHD and PMDD are complex and arise from multiple neurotransmitter pathway disruptions - not to mention the added neuroinflammation. Saffron extract targets the full picture of these disruptions and can provide overlapping relief for those with comorbid ADHD and PMDD.
Many in our community manage both ADHD and PMDD, and report that DITTO helps with both. This is why.
The Dose in DITTO
DITTO contains the exact dose of saffron extract tested in each clinical trial in this article (30 mg), with more than enough bioactives to impact mood. For those suffering with ADHD, PMDD, or both, DITTO could be the perfect addition to your daily routine.
References:
1. Broughton T, Lambert E, Wertz J, Agnew-Blais J. Increased risk of provisional premenstrual dysphoric disorder (PMDD) among females with attention-deficit hyperactivity disorder (ADHD): cross-sectional survey study. Br J Psychiatry. 2025
2. Dorani et al. Prevalence of hormone-related mood disorder symptoms in women with ADHD. J Psychiatr Res. 2021
3. Lin et al. Comorbid Attention Deficit Hyperactivity Disorder in Women with Premenstrual Dysphoric Disorder. J Womens Health (Larchmt). 2024
4. Blasco-Fontecilla H, Moyano-Ramírez E, Méndez-González O, Rodrigo-Yanguas M, Martin-Moratinos M, Bella-Fernández M. Effectivity of Saffron Extract (Saffr'Activ) on Treatment for Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): A Clinical Effectivity Study. Nutrients. 2022
5. Baziar S, Aqamolaei A, Khadem E, et al. Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study. J Child Adolesc Psychopharmacol. 2019;29(3):205-212
6. Pazoki B, Zandi N, Assaf Z, Moghaddam HS, Zeinoddini A, Mohammadi MR, et al. Efficacy and safety of saffron as adjunctive therapy in adults with attention-deficit/hyperactivity disorder: A randomized, double-blind, placebo-controlled clinical trial. Advances in Integrative Medicine. 2022
7. Khaksarian M, Ahangari N, Masjedi-Arani A, Mirr I, Jafari H, et al. A Comparison of Methylphenidate (MPH) and Combined Methylphenidate with Crocus sativus (Saffron) in the Treatment of Children and Adolescents with ADHD: A Randomized, Double-Blind, Parallel-Group, Clinical Trial.Iran J Psychiatry Behav Sci. 2021
8. Seyedi-Sahebari S, Farhang S, Araj-Khodaei M, et al. The Effects of Crocus sativus (Saffron) on ADHD: A Systematic Review. J Atten Disord. 2024
9. Rajabi F, Rahimi M, Sharbafchizadeh MR, Tarrahi MJ. Saffron for the Management of Premenstrual Dysphoric Disorder: A Randomized Controlled Trial. Adv Biomed Res. 2020
10. Chauhan S, Tiwari A, Verma A, Padhan PK, Verma S, Gupta PC. Exploring the Potential of Saffron as a Therapeutic Agent in Depression Treatment: A Comparative Review. Yale J Biol Med. 2024
11. Matraszek-Gawron R, Chwil M, Terlecki K, Skoczylas MM. Current Knowledge of the Antidepressant Activity of Chemical Compounds from Crocus sativus L. Pharmaceuticals (Basel). 2022;16(1):58.
12. Siddiqui SA, Ali Redha A, Snoeck ER, et al. Anti-Depressant Properties of Crocin Molecules in Saffron. Molecules. 2022;27(7):2076.
13. Mohajeri S.A., Sepahi S., Azam A.G. Chapter 27—Antidepressant and antianxiety properties of saffron. In: Koocheki A., Khajeh-Hosseini M., editors. Saffron Science, Technology and Health. Woodhead Publishing; Cambridgeshire, UK: 2020. pp. 431–444
14. Abedi A, Ghobadi H, Sharghi A, Iranpour S, Fazlzadeh M, Aslani MR. Effect of saffron supplementation on oxidative stress markers (MDA, TAC, TOS, GPx, SOD, and pro-oxidant/antioxidant balance): An updated systematic review and meta-analysis of randomized placebo-controlled trials. Front Med (Lausanne). 2023
15. Anaeigoudari F, Anaeigoudari A, Kheirkhah-Vakilabad A. A review of therapeutic impacts of saffron (Crocus sativus L.) and its constituents. Physiol Rep. 2023
16. Sacher J, Zsido RG, Barth C, et al. Increase in Serotonin Transporter Binding in Patients With Premenstrual Dysphoric Disorder Across the Menstrual Cycle: A Case-Control Longitudinal Neuroreceptor Ligand Positron Emission Tomography Imaging Study. Biol Psychiatry. 2023.
17. da Silva BS, Grevet EH, Silva LCF, Ramos JKN, Rovaris DL, Bau CHD. An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder. Discov Ment Health. 202318.
18.Cheng M, Jiang Z, Yang J, et al. The role of the neuroinflammation and stressors in premenstrual syndrome/premenstrual dysphoric disorder: a review. Front Endocrinol (Lausanne). 2025
19. Schnorr I, Siegl A, Luckhardt S, et al. Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome. Transl Psychiatry. 2024
